With the explosion of genetically engineered mouse models, there are enormous opportunities for mouse pathobiologists in biomedical research. The Principal Investigator's career objectives are to become a more independent and successful mouse pathobiology researcher and to use existing skills as well as those developed through this proposal to mentor the next generation of mouse pathobiologists. His growth as a scientist has been hindered by time constraints associated with service, administrative and teaching responsibilities. This award will provide release from some of these responsibilities and redistribution of time in others so that he will have more focused and intensive research time. The candidate is very well qualified for this award by virtue of his extensive background in training and pathology, his experience in both independent and collaborative research and his environment which facilitates and promotes mouse pathobiology research and training. This environment includes a Comparative Medicine Training Program, a world-renowned Research Animal Diagnostic Laboratory, a Comparative Medicine Research Center and one of four Mutant Mouse Regional Resource Centers. Long-term research goals include unraveling the mechanisms of chronic intestinal inflammatory disease so that ultimately novel prevention and treatment strategies can be developed. The objectives of this proposal focus on differences seen between males and females in inflammatory diseases of the intestinal mucosa. The following specific aims will be employed in pursuit of these objectives: 1) determine what cell types characterize mucosal inflammation caused by H. hepaticus in the A/J mouse 2) assess the role of the gonadal steroid hormones, estrogen and testosterone, in pathogenesis of bacterial initiated mucosal inflammation and 3) assess the role of estrogen signaling of immune cells via estrogen receptor alpha (ERe0 and beta (ERL3) in mucosal inflammation. These projects will provide an ideal forum for the training of individuals in mouse pathobiology and enable them to initiate careers in research and become leaders in this field.